Aprea Therapeutics has secured breakthrough therapy designation from the US Food and Drug Administration (FDA) for its lead molecule APR-246 in combination with chemotherapy drug azacitidine in myelodysplastic syndromes (MDS).
The APR-246, azacitidine combination has been granted breakthrough therapy status for the treatment of myelodysplastic syndromes in patients having a susceptible TP53 mutation.
Myelodysplastic syndromes are defined as a group of cancers in which bone marrow cannot generate adequate numbers of healthy blood cells.
According to Aprea Therapeutics, nearly 30-40% of patients having the condition progress to acute myeloid leukaemia and mutation of the p53 tumour suppressor protein is believed to contribute directly to disease progression and a poor overall prognosis.
Considered to be the most commonly mutated gene in human cancer, the p53 tumour suppressor gene occurs in about 50% of all human tumours. The mutations are usually related to resistance to anti-cancer drugs and poor overall survival, thereby representing a significant unmet medical need in cancer treatment, said Aprea Therapeutics.
Aprea Therapeutics claimed that APR-246 has shown reactivation of mutant and inactivated p53 protein by restoring wild-type p53 conformation and function, thereby triggering programmed cell death in human cancer cells.
As per the company, pre-clinical anti-tumour activity has been observed with APR-246 in myelodysplastic syndromes, acute myeloid leukaemia, ovarian cancer, and other solid and haematological cancers.
The breakthrough therapy designation from the FDA is given to help accelerate the development and review of a drug candidate which is intended for the treatment of a serious or life-threatening disease or condition. The designation is granted by the regulator when preliminary clinical evidence shows that the drug could deliver a significant improvement over existing therapies on one or more clinically significant endpoints.
Aprea Therapeutics CEO Christian Schade said: “Outcomes for MDS patients with a TP53 mutation are poor and there are no current therapeutic options specifically for these patients. We look forward to continued interaction with FDA regarding our ongoing Phase 3 clinical study and our clinical development program to advance APR-246.”
The small molecule candidate of Aprea Therapeutics had also secured orphan drug designation from the FDA for myelodysplastic syndromes apart from orphan drug status in the European Union for myelodysplastic syndromes, acute myeloid leukaemia, and ovarian cancer.